Safety and Incidence of Cardiovascular Events in Chinese Patients with Acute Coronary Syndrome Treated with Ticagrelor: the 12-Month, Phase IV, Multicenter, Single-Arm DAYU Study

Runlin Gao,Yan Wang,Guohai Su,Huanyi Zhang,Zuyi Yuan,Lijun Shen,Maria Leonsson-Zachrisson,Hengliang Liu,Yang Zheng,Yong Wang,Aidong Zhang,Yaling Han,Zhirong Wang,Yongjian Wu,Lei Liu

doi:10.1007/s10557-018-6772-3

Abstract

PurposeTicagrelor is an orally administered, reversibly binding, direct-acting P2Y12 receptor antagonist previously evaluated in several phase III trials. This phase IV, multicenter, single-arm trial assessed the safety and incidence of cardiovascular (CV) events with ticagrelor in Chinese patients experiencing an acute coronary syndrome (ACS).MethodsPatients hospitalized with an ACS received ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) plus low-dose aspirin (75–100 mg/day) for up to 12 months. Safety was evaluated via PLATO-defined bleeding events, adverse events (AEs), serious AEs, and laboratory measurements. The incidence of major CV events was also evaluated.ResultsThe safety population included 2001 patients. During ticagrelor treatment, 426 (21.3%) patients had at least one PLATO-defined bleeding AE, mainly minimal bleedings (n = 333). Major bleeding events occurred in 27 (1.3%) patients, including fatal/life-threatening bleeding in 17 (0.8%) patients and other major bleeding in 11 (0.5%) patients, with a Kaplan-Meier estimate of patients with the event (95% CI) of 1.6% (1.1–2.3%). In total, 784 (39.2%) patients had at least one non-bleeding AE, the majority of which were mild in severity. The composite endpoint of CV death, myocardial infarction, and stroke occurred in 83 (4.1%) patients.ConclusionsTicagrelor plus low-dose aspirin for up to 1 year was associated with a low rate of major bleeding events and a low incidence of major CV events (CV death, myocardial infarction, stroke) in Chinese patients with ACS. The overall safety profile of ticagrelor in this population was in line with current prescribing information.

Highlights

~ 230 million individuals have cardiovascular disease (CVD) in China [1]
The DAYU study described the safety and rate of CV events during ticagrelor treatment in a large cohort of Chinese acute coronary syndrome (ACS) patients, a population with limited data when ticagrelor was approved in China in 2012
The DAYU study demonstrated that ticagrelor 90 mg twice daily with low-dose aspirin for up to 1 year is associated with a low incidence of major bleeding events and serious adverse event (SAE), and a low incidence of major CV events in Chinese patients with ACS

Summary

Introduction

~ 230 million individuals have cardiovascular disease (CVD) in China [1]. Chinese patients experiencing an acute coronary syndrome (ACS)—encompassing unstable angina, non-ST elevation myocardial infarction (NSTEMI), and ST elevation myocardial infarction (STEMI)—have a high mortality rate [2, 3]. Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor (ticagrelor, clopidogrel or prasugrel for ≥ 12 months) represents the cornerstone of ACS management [5,6,7,8,9]. Ticagrelor with low-dose aspirin is approved in more than 100 countries (including China) to reduce the rate of CV death, myocardial infarction (MI), and stroke in ACS patients (180 mg loading dose 90 mg twice daily [b.i.d] for the first year post-ACS event) [13]. In some countries and regions (e.g., USA, Japan, Hong Kong, and EU countries), ticagrelor is approved to reduce the rate of CV death, MI, and stroke in patients with a history of MI (60 mg b.i.d from 1 year post-MI)

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Conclusion